Effect of Duloxetine and Venlafaxine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol: A Three-phase Randomized Balanced Cross-over Study in Healthy Volunteers

NCT01443520 | Completed Phase 4

• 2 other identifiers: 97/180/20112011-003259-20
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. After oral administration, tramadol is rapidly and almost completely absorbed. Tramadol is extensively metabolised by O- and N-demethylation, which are catalysed by the liver CYP-450 enzymes. O-desmethyltramadol is an active metabolite and its formation is catalysed by CYP2D6. This study is aimed to investigate the possible interaction of oral tramadol with duloxetine and venlafaxine. Duloxetine is known to inhibit CYP2D6. Twelve healthy male or female adult non-smoking volunteers aged 18-40 years with body weights within ±15% of the ideal weight for height are taken into the study. Primary endpoints of the study are plasma concentrations of tramadol and its metabolites.

Conditions

Healthy

Keywords

Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• Concentration of tramadol and its metabolites in plasma

  0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours after administration of tramadol

Secondary Outcomes (3)

• Serotonin concentrations

  0, 4 and 8 hours after tramadol administration

• Pharmacodynamic effects

  1, 2, 3, 4, 5, 6, 8, 10, 12 hours after administration of tramadol

• Analgesia

  1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the administration of tramadol

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Duloxetine

ACTIVE COMPARATOR

Drug: Duloxetine

Venlafaxine

ACTIVE COMPARATOR

Drug: Venlafaxine

Interventions

Placebo DRUG

The subjects will be given orally placebo twice a day for 8 days prior to the study.

Placebo

Duloxetine DRUG

The subjects will be given orally duloxetine 30mg twice a day for 8 days prior to the study.

Duloxetine

Venlafaxine DRUG

The subjects will be given orally venlafaxine 37,5mg twice a day for 8 days prior to the study.

Venlafaxine

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers
• Age 18-40
• Body weight within ±15% of the ideal weight for height

You may not qualify if:

• A previous history of intolerance to the study drugs or to related compounds and additives
• Concomitant drug therapy of any kind for at least 14 days prior to the study
• Existing or recent significant disease
• History of hematological, endocrine, metabolic or gastrointestinal disease, including gut motility disorders
• History of asthma or any kind of drug allergy
• Previous or present alcoholism, drug abuse, psychological or other emotional problems that are likely to invalidate informed consent, or limit the ability of the subject to comply with the protocol requirements
• A positive test result for urine toxicology
• A "yes" answer to any one of the Abuse Questions
• Pregnancy or nursing
• Donation of blood for 4 weeks prior and during the study
• Special diet or life style conditions which would compromise the conditions of the study or interpretation of the results
• Participation in any other studies involving investigational or marketed drug products concomitantly or within one month prior to the entry into this study
• Smoking for one month before the start of the study and during the whole study period
• Any history of coagulation abnormality, also in first degree relatives

Sponsors & Collaborators

• Turku University Hospital: lead

Study Sites (1)

Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital

Turku, Finland

Location

MeSH Terms

Interventions

Duloxetine Hydrochloride; Venlafaxine Hydrochloride

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2011
• First Posted: September 29, 2011
• Study Start: October 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: May 22, 2012

Record last verified: 2012-05

Locations

FI (1)